Figure 3. Pharmacology of 6β-cinnamoylmorphinamine 8a.

(A) Analgesia: Cumulative dose-response curves were carried out on groups of mice (n = 10) with 8a at the indicated doses (s.c.) and analgesia tested 30 min later at peak effect. The ED₅₀ value was 3.13 ± 1.09 mg/kg in CD1 mice by using the radiant heat tail-flick assay. Results were evaluated as %MPE [(observed latency − baseline latency)/(maximal latency − baseline latency)] and shown as the average of each group (n = 10). (B) Sensitivity of 8a to opioid antagonists: Groups of mice (n = 6) received a fixed dose of 8a (5 mg/kg, s.c.) alone or with NorBNI (10 mg/kg, s.c.), β-FNA (40 mg/kg, s.c.), NTI (20 mg/kg, s.c.). β-FNA and NorBNI were given 24h before 8a while NTI was given 15 min before 8a. Tail flick analgesia was measured 30 min after 8a. Similar results were observed in two independent replications. 8a analgesia is insensitive to NorBNI while analgesia is partially antagonized by both β-FNA and NTI (ANOVA followed by Bonferroni multiple comparison test (p < 0.05). (C) Respiratory rate. Animals were randomly assigned to receive saline (n = 3), 8a (24 mg/kg, n = 3), or morphine (20 mg/kg, n = 3). Each animal’s baseline average breath rate was measured every 5 min for 25 min before drug injection, and breath rates after drug injection are expressed as a percent of baseline. 8a did not depress respiratory rate and was not significantly different from saline at any time point, whereas morphine decreased respiratory depression in comparison with both saline and 8a (p < 0.05) as determined by repeated-measures ANOVA followed by Bonferroni multiple-comparison test.